Twenty years after entering the University of Pittsburgh as an undergraduate biological sciences major, Bruce Nmezi (BS, A&S ’07; PhD, HUGEN ’19) traded an on-campus laboratory for one at Krystal Biotech Inc., a Pittsburgh-based company focused on developing genetic medicines for deadly and rare diseases.
More than 30 million people in the United States have one of at least 7,000 rare genetic diseases. Most are so rare that no company is willing to spend years developing a gene therapy that so few people would need.
Founded in 2016, Krystal Biotech obtained U.S. Food and Drug Administration approval for the first and only topical gene therapy gel for dystrophic epidermolysis bullosa (DEB), a rare disorder linked to mutations in the COL7A1 gene, which affects the production of type VII collagen.
People with DEB have extremely fragile skin that blisters and tears easily, even with minor trauma. In mild cases, blistering mostly affects hands, feet, knees and elbows. Severe cases, however, can lead to widespread blistering, vision issues and other serious health problems, including skin cancer.
“It’s been more than 20 years since the completion of the Human Genome Project and technology has caught up. What people used to imagine can now be possible,” says Nmezi, crediting his Pitt education with giving him the foundation necessary for success throughout his scientific journey.
In 2012, Nmezi began working as a laboratory technician in the Department of Human Genetics at Pitt’s School of Public Health, running western blot analyses to separate proteins and conducting assays using quantitative polymerase chain reaction to measure gene expression and identify mutations. In the following years, he completed a doctorate in human genetics and a postdoctoral fellowship on the neurobiology of disease funded by Pitt’s Center for Neuroscience.
While problem solving underlies both academic research and the biotech industry, motive, approach and tempo diverges, notes Nmezi. “Industry is go-go-go, focused on data and results,” he says. “In academia, it’s ‘This is interesting, let’s take a look at it.’”
As a researcher in the Department of Human Genetics, Nmezi studied a gene encoding a cellular nuclear protein known as lamin B1, the duplication of which leads to autosomal dominant leukodystrophy (ADLD), a devastating and fatal progressive neurological disease. He is an author on 13 peer-reviewed publications with more in the pipeline, including a first authorship on a February 2025 publication in the high-impact journal Nature Communications that showed, for the first time, that a gene “silencer” in junk DNA can spare some people who have an extra copy of lamin B1 from the disease.
“It was a completely novel hypothesis. I don’t think it would have been possible without Bruce, because we started off with a completely new area of work using CRISPR (clustered regularly interspaced short palindromic repeats) gene editing, which we had never done in the lab before, says Quasar Padiath, MBBS, PhD, human genetics chair and the paper’s senior author. “Bruces is a very rigorous scientist with impeccable integrity. You know that if he does an experiment, you can trust that it’s right.”
-Michele Baum